Previous studies performed in collaboration with our laboratory have clearly demonstrated that passive administration of goat anti-FLV gp71 IgG to AKR mice during a narrow neonatal therapy 'window' effectively delays or prevents the later development of leukemia in a majority of animals. Immune IgG therapy is accompanied by (1) a suppression of ecotropic MuLV viremia, (2) the development of host anti-viral humoral immune responses, and (3) a dramatic shift toward the nonthymic form of the disease in the few treated animals which eventually develop leukemia. The current research is intended to examine the mechanism(s) operative in our therapy model in order to better understand early events which are crucial to the process of leukemogenesis. These studies will focus upon alterations in both virus expression and immune responsiveness as they relate to our therapy protocols. The influence of serum therapy upon the kinetics of virus expression during the first weeks of life will be examined. Virus expression in various organs will be monitored by infectious cell center (ICC) assays for ecotropic MuLV. Specific cell populations harboring endogenous virus will be isolated and identified by cell depletion techniques as well as fluorescence activated cell sorting (FACS) in an effort to identify the potential immunotherapeutic target of our IgG therapy. We will examine the basis of a narrow 'therapy window' comprising the first 4 days of life during which time therapy must be initiated. Since this time coincides with a critical period of immune ontogeny we will conduct additional studies to determine the effect of serum therapy upon hematopoiesis, lymphoid trafficking, generalized immunocompetence and specific anti-viral immune responsiveness. We will pay particular attention to alterations in the thymus in an effort to better pinpoint thymic involvement in the leukemogenic process. We will examine similar immunologic and virologic parameters in various generations of AKR mice bred from treated, antibody-positive, virus-negative parents. Finally, we will begin to explore the use of homologous monoclonal anti-viral antibodies as treatment modalities against AKR leukemias, utilizing the knowledge gained with heterologous serum therapy for comparison.